Inflammation plays a pivotal role in all stages of atherosclerosis. Weight loss appears to be the best nonpharmacologic modality to reduce inflammation. Intervention trials convincingly demonstrate that weight loss reduces biomarkers of inflammation, such as C-reactive protein. Limited studies have shown that certain dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation. Most of the studies with fish oil supplementation have shown null effects, and conflicting results have been reported with saturated and trans fatty acids. Much further research is needed to define the role of individual dietary factors on the biomarkers of inflammation and the mechanism of the anti-inflammatory effects of weight loss.